阿佩林
斑马鱼
血管生成
细胞生物学
背主动脉
生物
信号转导
基因敲除
Notch信号通路
转录因子
表型
癌症研究
细胞培养
受体
干细胞
遗传学
基因
造血
作者
Christian S. M. Helker,Jean Eberlein,Kerstin Wilhelm,Toshiya Sugino,Julian Malchow,Annika Schuermann,Stefan Baumeister,Hyouk-Bum Kwon,Hans-Martin Maischein,Michael Potente,Wiebke Herzog,Didier Y.R. Stainier
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2020-09-21
卷期号:9
被引量:54
摘要
To form new blood vessels (angiogenesis), endothelial cells (ECs) must be activated and acquire highly migratory and proliferative phenotypes. However, the molecular mechanisms that govern these processes are incompletely understood. Here, we show that Apelin signaling functions to drive ECs into such an angiogenic state. Zebrafish lacking Apelin signaling exhibit defects in endothelial tip cell morphology and sprouting. Using transplantation experiments, we find that in mosaic vessels, wild-type ECs leave the dorsal aorta (DA) and form new vessels while neighboring ECs defective in Apelin signaling remain in the DA. Mechanistically, Apelin signaling enhances glycolytic activity in ECs at least in part by increasing levels of the growth-promoting transcription factor c-Myc. Moreover, APELIN expression is regulated by Notch signaling in human ECs, and its function is required for the hypersprouting phenotype in Delta-like 4 (Dll4) knockdown zebrafish embryos. These data provide new insights into fundamental principles of blood vessel formation and Apelin signaling, enabling a better understanding of vascular growth in health and disease.
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